Estimation of the true rates of degradation of proteins in vivo using labeled amino acids is complicated by extensive reutilization of amino acids. The amino acid 3-methylhistidine is a constituent of actin and some myosins. It is not reutilized after its release and, therefore, measurement of the rate of release of 3-MeH from these proteins should provide a true estimate of the rates of actin and myosin breakdown. The determination of suitable C14-labelled precursors for labelling 3-methylhistidine in vivo is being studied and the urinary excretion of 3-methylhistidine is also being evaluated in relation to muscle protein turnover. Successful development of this new approach to the estimation of muscle protein degradation rates in vivo will be followed by application of the method to studies of changes in muscle protein turnover under various physiological and pathological conditions.